DESCRIPTION (Verbatim from applicant's abstract): Long-range goals and rationale: In mammals, information about the visual world is transmitted from the eye to more than 10 distinct brain nuclei by at least 20 different retinal ganglion cell (GC) classes. Both the underlying retinal circuitry responsible for these GC response properties and the function in vision of the various GC classes remains poorly known. The well-known diversity of GC classes in rabbit makes it the species of choice for the study of mammalian GC mechanisms. Differential diagnosis of eye diseases (many of which involve retina GCs) will depend critically on understanding GC receptive field mechanisms. The project will focus on directional selectivity as an example of a complex GC receptive field properties including determining how amacrine cell inputs may mediate correlated firing among directionally-selective (DS) and other GC types. Research design and methods: The proposed study will use extracellular and whole-cell patch recording of GCs in the isolated rabbit retina preparation to understand the retinal circuitry neurotransmitters and biophysical mechanisms underlying the responses of DS GCs and other complex receptive field GCs in rabbit. Specific aims of this research application are to: (1) relate the computational properties of DS GCs to a retinal circuit model in which specific inputs can be associated with specific response features such as response invariance with respect to contrast, motion, distance, and velocity; (2) determine the direct inputs to the DS GC by whole-cell patch-clamp voltage recordings and determine how those inputs may interact within the GC dendritic tree during whole-cell current clamp modulation of responses to photic input; and (3) investigate the "meaning" or sensory code for the DS and other GC outputs via dual recordings using models for combining the outputs of multiple cells to extract additional information from the outputs, such as the occurrence of synchronized firing for extended stimuli moving in the cells' preferred direction.